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HIV Lessons From The Mississippi Baby

The news in July that HIV had returned in a Mississippi toddler after a two-year treatment-free remission dashed the hopes of clinicians, HIV researchers and the public at large tantalised by the possibility of a cure.

But a new commentary by two leading HIV experts at Johns Hopkins argues that despite its disappointing outcome, the Mississippi case and two other recent HIV “rebounds” in adults, have yielded critical lessons about the virus’ most perplexing – and maddening – feature: its ability to form cure-defying viral hideouts.

Writing in the Aug. 28 issue of the journal Science, HIV research duo Robert Siliciano, M.D., Ph.D., and Janet Siliciano, Ph.D., note that such “failures” are in fact stepping stones to new understanding of what “cure” may look like and new therapies that tame the virus into long-term remission.

“Heartbreaking as these three cases are clinically, they provide a dramatic illustration of the real barrier to an HIV cure and illuminate important therapeutic strategies,” says Robert Siliciano. “This is not the end of the story but the beginning of a new chapter.”

The 27-month off-treatment remission experienced by the Mississippi toddler is, in and of itself, a laudable therapeutic goal, the Silicianos write, and is what cure of HIV may look like in the foreseeable future. Finding ways to induce long-term remission and to closely monitor its course will be the next frontier in HIV treatment, they write.

The ability to put the virus in remission and go off treatment for months or years at a time is an important goal, because it can spare HIV-infected people from a lifetime of daily antiviral regimens, which can be difficult to tolerate and hard to follow. Failure to comply with the strict treatment protocol, which occurs often, can lead to viral mutations that make HIV resistant to drugs.

All three cases, the Silicianos write, also reaffirm that the single most important hurdle to eradicating HIV is a tiny but extremely stable pool of virus tucked away in a handful of immune cells known as memory CD4+ T cells.

Memory T cells are the immune system’s combat-trained sentinels, responsible for fighting invaders they have encountered in the past. Much of the time, memory T cells lie dormant and become active only when the body is invaded by old foes they are specifically trained to recognize. HIV invades memory T cells early in the infection, and as long as the T cells lie quiet, so does HIV inside them. However, as soon as memory T cells get stirred up by an invader, the HIV DNA inside them wakes up, cranks out new virus and reignites infection. Because antiviral drugs work only against actively replicating virus, such silent viral hideouts remain out of therapy’s reach. Thus, reducing the number of latently infected cells or precluding their formation altogether is an important and – as the three recent cases suggest – realistic strategy, the Silicianos say.

“These cases paint several clinical scenarios where a substantial reduction of viral reservoirs would allow some patients to come off treatment for prolonged yet uncertain periods of time, but they also raise the critical question of how to best monitor them for relapse so they can resume therapy swiftly when the virus rebounds,” says Janet Siliciano.